Soluble interleukin-6 receptor a inhibits the cytokine-induced fractalkine/CX3CL1 expression in human vascular endothelial cells in culture

Soluble form of IL-6 receptor alpha (sIL-6R) is known to serve as an agonis t, without exogenous IL-6, on endothelial cells which do not express IL-6R but have only IL-6 receptor beta chain, gp130. We investigated the effect o f sIL-6R on fractalkine expression in human umbilical vein endothelial cell s (HUVECs) in culture. sIL-6R markedly inhibited HUVEC fractalkine/CX3CL1 e xpression induced by interleukin (IL)-1 alpha, tumor necrosis factor (TN-F) -alpha, or interferon (IFN)-gamma. IL-1 alpha -induced fractalkine expressi on was inhibited by sIL-6R in time- and concentration-dependent manners. Th e experiment using actinomycin D indicated that sIL-6R lowered the stabilit y of fractalkine mRNA. The inhibitory effect of sIL-6R was reversed by anti -gp130 neutralizing antibody. sIL-6R inhibited adhesion of mononuclear cell s (MNCs) to HUVEC monolayers stimulated with IFN-gamma, but it did not inhi bit the adhesion to monolayers stimulated with IL-1 alpha. MNC chemotactic activity of conditioned medium of HUVEC stimulated with IL-1 alpha or IFN-g amma was inhibited by cotreatment with sIL-6R. sIL-6R may play a regulatory role in immune responses by modulating the interaction between leukocytes and the vascular endothelium. (C) 2001 Academic Press.